PROJECT SUMMARY (COOPER CITEK): ?Secondary-sphere interactions in the activation of dinitrogen and other small molecules by synthetic models of the nitrogenase FeMo cofactor? Nitrogen-based fertilizers are a crucial component of feeding the Earth?s expanding population. Not only do fertilizers allow modern agricultures sustain more than 7 billion people, they help farmers to produce more food with less land, thereby limiting the environmental impacts of excess water consumption or of clearing habitats critical to diverse ecosystems. Today, the Haber-Bosch process supplies enormous quantities of synthetic ammonia from atmospheric dinitrogen. However the total expense of this process amounts to 2% of global energy consumption, 4% of natural gas, and the associated impact of greenhouse gases produced. Certain bacteria and archaea are able to derive ammonia from atmospheric dinitrogen for the benefit of themselves and the ecologies of which they are members. Biological nitrogen fixation is known to be facilitated by an iron-sulfur cofactors within conserved nitrogenase enzymes. These cofactors (the most well-known being the FeMo cofactor) both bind and reduce dinitrogen, with equivalents of biologically-derived protons and electrons and ATP hydrolysis. While dinitrogen fixation represents a significant cost to competent organisms, this input might establish a lower bound to energetic investment for nitrogen fixation. However the operative mechanism of nitrogenase FeMo cofactor is still debated at the fundamental, chemical level. This proposal aims to probe the mechanistic significance of conserved residues in the secondary coordination sphere of the FeMo cofactor, namely a histidine that is thought to facilitate hydrogen bonding or proton shuttling during catalysis. We will employ synthetic models to mimic a hypothesized dinitrogen binding site that is adjacent to the conserved histidine and to study the pathways of proton-coupled reduction of small molecules by these models. Molecular iron complexes incorporating secondary-sphere hydrogen-bonding functionality (histidine analogs) can be accessed by known preparations and may allow for the stabilization of reactive species on-path toward dinitrogen fixation or, conversely, for the enhancement of catalytic dinitrogen reduction. In the former case, we may be able to characterize previously unobserved intermediates of the reaction of protons with reduced iron-dinitrogen species (by 57Fe Mssbauer, EPR, X-ray crystallography, electrochemistry, etc.) and their stepwise conversion to other known complexes. In the latter case, we may probe the chemical motifs that impart the FeMo cofactor with such facility for a difficult small-molecule transformation by examining catalysis kinetics, energetics, and the intimate step-by-step order of proton- and electron-additions (by reaction rates, electrochemistry, proton dependences, etc.). It is hoped that hydrogen- bonding structures may even permit milder reagents for homogeneous dinitrogen reduction. If molecular iron systems are to become essential technologies for the future, they must be understood at the fundamental level and must be compatible with sustainable sources of energy.